Continuous arteriovenous hemodialysis (CAVHD) is being used increasingly as the major form of renal replacement therapy for critically ill patients with acute renal failure (ARF). Generally, the procedure has required systemic anticoagulation utilizing heparin or, in a few cases, prostacyclin to maintain filter patency (1). Although heparin is removed by CAVHD membranes, systemic anticoagulation is usually unavoidable and has been associated with an increased incidence of bleeding (2). In order to circumvent this problem regional heparin anticoagulation has been tried, but this has not gained widespread acceptance due to the difficulty in accurately adjusting protamine doses (3). Similarly, CAVHD has been attempted with frequent saline flushes through the filter, but it has been difficult to keep the filter patent for longer than 24 hours. Although regional citrate anticoagulation has been utilized for conventional hemodialysis (3) it has not previously been used for CAVHD. Citrate was previously not suitable for CAVHD due to the problem of accumulation of citrate and the products of citrate metabolism when used continuously over periods of many hours or days, and the limitation on the rate of removal of these products given the low dialysate flow rates employed in CAVHD.
Thus, there exists a need for an anticoagulant which can be effective in CAVHD but not produce the increased bleeding associated with heparin. This need is satisfied by the present invention due to the development of a technique employing sodium citrate as a regional anticoagulant for CAVHD (citrate CAVHD) which results in smooth removal of excess water, electrolytes and catabolic toxins without requiring systemic anticoagulation. Citrate is infused at the origin of the extracorporeal circuit, and the citrate-calcium chelate is removed by diffusion across the membrane. The metabolic consequences of the sodium citrate load are compensated for by the use of a special dialysate containing no alkali, subnormal sodium concentration, and no calcium. Calcium homeostasis is restored by a peripheral infusion of calcium chloride.
This system achieves excellent patency and longevity of the standard CAVHD filter without any systemic anticoagulant effect. We have successfully utilized citrate CAVHD for two thousand hours in eleven critically ill patients without any hemorrhagic complications, whereas one third of patients treated with standard heparin anticoagulated CAVHD (heparin CAVHD) developed complications related to heparinization. Citrate CAVHD can replace heparin anticoagulation and is especially advantageous in seriously ill ARF patients who are at higher risk of bleeding.